The proposed program of research deals with a group of chemical agents known or suspected to occur in foods, and a set of biological systems expected to interact with the agents in defined manners. Specific biological systems include in vitro and in vivo types; namely, microorganisms and mammalian cell cultures, and neonatal, young and adult mammals. The in vitro responses will be used as a link between the study of the occurrence of agents in foods and model systems, and biological responses in animals. The types of in vitro responses to be investigated include cytotoxicity, mutagenicity, host-mediated mutagenicity and antimicrobial effects. The in vivo investigations will pay particular attention to interactions with macromolecular components and cellular organelles; acute responses in neonatal animals; and long-term effects (carcinogenesis, mutagenesis and others) following exposure to agents at various ages from in utero to post-weaning periods. Specific agents to be investigated include N-nitroso compounds, phenolic compounds from wood smoke, lipid peroxides and reaction products of lipid peroxides and constituents of food such as proteins and amino acids. The proposed program has several major goals. Their accomplishment would result in significant contributions to knowledge in new and existing problem areas of the chemistry of non-nutritive chemicals in foods, their interactions with cells and the mechanism by which they produce undesirable biological effects. Major emphasis is also placed on the adaptation and application of such fundamental information to the problems of evaluating the extent to which environmental chemicals pose health risks to man. Where ever possible, attempts will be made to improve existing methods as to devise new methodology to facilitate evaluation of such risks.